The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated herein by reference and set forth in the Bibliography.
Integrin-mediated cell adhesion regulates a multitude of cellular responses including proliferation, survival and cross-talk between different cellular signalling pathways1. Thus far, integrins have been mainly shown to convey permissive signals enabling anchorage-dependent receptor tyrosine kinase signalling2,3. In response to cell adhesion, integrins activate certain cytoplasmic signalling pathways directly and modulate signalling by growth factor receptors. indirectly. The cytoplasmic domains of integrins are essential in mediating these functions4-7. However, they lack intrinsic catalytic activity and require interactions with cytoplasmic proteins for signalling. Although collagen is a very abundant protein in the human body, relatively little is known about signalling of the four collagen binding integrins, α1β1, α2β1, α10β1 and α11β1. Integrin α1β1 is a receptor for collagens and laminins. Its a-subunit has been shown to associate with caveolin-1 and thus recruit signalling adaptor protein Shc8. This in turn leads to the activation of the mitogen-activated protein kinase pathway and increased survival and proliferation of fibroblasts on collagen9. In addition, the conserved region found in all integrin a-cytoplasmic tails has been shown function in focal adhesion assembly via the association with paxillin, talin and focal adhesion kinase10. However, thus far signalling pathways specifically activated by α1 integrin alone have remained unidentified.